Development of biosensors is an active field, with applications in lab-on-a-chip, diagnostics of infectious diseases, cancer diagnostics, environment monitoring, biodetection and other fields. One strategy used for selective identification of a biological target is to preselect a probe that has a unique affinity for the target or that can uniquely interact with or hybridize the target, using a “lock and key” approach. In this approach, one needs a platform to support the probe and a recognition element that can sense presence of the desired interaction between the probe and the target. The interaction result can manifest itself optically (using dyes, quantum dots for example) or electrically. The platform design and configuration may vary, depending on whether optical or electrical interaction is used. Electrical readout biosensors have gained much attention because, in principle, they can be made more compact than optical technologies.
Advances in microfabrication and related technologies have aided development of electrical readout based biosensors. One popular approach is a bio-field effect transistor (Bio-FET), wherein a probe molecule is functionalized in the gate region of a three-terminal transistor [Schafer et al, “Time-dependent observation of individual cellular binding events to field-effect transistors,” Biosensors and Bioelectronics. Vol 24 (2009) pp. 1201-1208]. When the probe-target hybridization takes place, a shift occurs in the threshold voltage of the current-voltage curve from the corresponding curve before hybridization. Wafer scale fabrication of Bio-FETs can assure reasonable unit cost for each sensor.
Another competing electrical readout technology relies upon use of an electrode instead of a transistor. In this approach, the electrode tip has an attached probe, and when hybridization with the target occurs, the generated signal will be transmitted by the electrode to a measurement circuit. A previous NASA Ames innovation [Jun Li et al, “Carbon Nanotube Nanoelectrode Array for Ultrasensitive DNA Detection,” Nano Letters, vol. 3 (2003) pp. 597-602] involves a nanoelectrode array consisting of an array of carbon nanofibers as individual nanoelectrodes, as illustrated in FIG. 1. Each nanofiber is a solid nanocylinder having a probe attached to it, and the array size, chip size and wafer size are controlled.
Other approaches have used various inorganic nanowires, such as silicon or oxide nanowires instead of carbon nanofibers; these nanowires are also solid cylinders [M. Meyyappan and M. Sunkara, “Inorganic Nanowires: Applications, Properties and Characterization,” Chap. 14, CRC Press, Baton Rouge, Fla., (2009)]. Others have used gold quantum dots, which are small solid spheres. The probe attachment is done on the tip of the cylinder or outer surface of the sphere for each of these approaches.
A more recent approach involves use of a nanopipette, which is a tiny hollow tube with probe molecule attached at a tapered end on the external surface. FIG. 2 illustrates a nanopipette configuration. M. Karhanek et al, “Single DNA Molecule Detection Using Nanopipettes and Nanoparticles,” Nano Letters, vol. 3 (2003) pp. 403-407] report use a quartz capillary which is drawn into a tiny pipette using a laser puller, with an inner diameter of about 50 nm. Probe functionalities chosen for a specified target are attached to the outside surface of the nanopipette tip. This approach provides a competitive technique for biosensing, when compared with the Bio-FET or any of the nanoelectrode approaches discussed above. One problem encountered is that pulling a pipette out of a glass capillary using a laser puller (or any other pulling approach) yields one pipette at a time. A feasible biosensing technology will require an array of nanopipettes, by analogy with the competing technologies of Bio-FETs arrays or nanoelectrodes arrays.
A useful approach would permit would formation of an array of nanopipettes with controllable diameters, densities and/or lengths.